Comparison of Global Gene Expression of Gastric Cardia and Noncardia Cancers from a High-Risk Population in China

Abstract

ObjectiveTo profile RNA expression in gastric cancer by anatomic subsites as an initial step in identifying molecular subtypes and providing targets for early detection and therapy.MethodsWe performed transcriptome analysis using the Affymetrix GeneChip U133A in gastric cardia adenocarcinomas (n = 62) and gastric noncardia adenocarcinomas (n = 72) and their matched normal tissues from patients in Shanxi Province, and validated selected dysregulated genes with additional RNA studies. Expression of dysregulated genes was also related to survival of cases.ResultsPrincipal Component Analysis showed that samples clustered by tumor vs. normal, anatomic location, and histopathologic features. Paired t-tests of tumor/normal tissues identified 511 genes whose expression was dysregulated (P<4.7E-07 and at least two-fold difference in magnitude) in cardia or noncardia gastric cancers, including nearly one-half (n = 239, 47%) dysregulated in both cardia and noncardia, one-fourth dysregulated in cardia only (n = 128, 25%), and about one-fourth in noncardia only (n = 144, 28%). Additional RNA studies confirmed profiling results. Expression was associated with case survival for 20 genes in cardia and 36 genes in noncardia gastric cancers.ConclusionsThe dysregulated genes identified here represent a comprehensive starting point for future efforts to understand etiologic heterogeneity, develop diagnostic biomarkers for early detection, and test molecularly-targeted therapies for gastric cancer.

Helicobacter pylori and Gastric Cancer

“…Differences could be identified for proximal versus distal gastric cancer of the intestinal type, especially when compared with diffuse-type neoplasias [150,151]. Lei et al [152] suggested a stratification into three different gastric cancer subtypes showing not only specific pathobiological characteristics but also remarkable differences concerning the response to treatment with either 5-fluorouracil or compounds targeting the PI3K-Akt-mTOR axis.…”

La importancia del sistema activador de plasminógeno en la patogénesis y progresión del cáncer gástrico

“…Two major types can be distinguished; the tumors located in the distal region (non-cardia cancer) and in the proximal region (cardia cancer) (McColl, 2006). These two anatomical subtypes are different in their etiology and epidemiology Derakhshan et al, 2008;Bertuccio et al, 2009;Wang et al, 2013). Some of the main differences between anatomical subtypes of GC have been addressed with more detail by previously published excellent reviews (McColl, 2006;Colquhoun et al, 2015;Huang, Sun, Fang, Zhou, & Zou, 2016).…”

Screening and Early Detection of Gastric Cancer

“…77 As of this writing, several basic science studies have been conducted for the molecular classification of gastric cancer in terms of prognostic factors, response to chemotherapy, distinct therapeutic targets, and diagnostic biomarkers. [78][79][80][81] However, most of these studies had a similar limitation of sample size or analyzing technique, and failed to show unique molecular characteristics that accounts for the epidemiologic or ethnic heterogeneity in clinical outcomes. Recently the Cancer Genome Atlas Research Network reported the comprehensive characterization of gastric cancer, which described the molecular evaluation of 295 primary gastric adenocarcinomas.…”